Bemfola (Solution) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

ATC Code

G03GA05 (Follitropin alfa)

Active Substance

Follitropin alfa (Rec.INN registered by WHO)

Dosage Forms

	Bemfola	Solution for subcutaneous injection 5.5 mcg/0.125 ml: pen-injectors 1, 5 or 10 pcs.
		Solution for subcutaneous injection 11 mcg/0.25 ml
		Solution for subcutaneous injection 16.5 mcg/0.375 ml
		Solution for subcutaneous injection 22 mcg/0.5 ml
		Solution for subcutaneous injection 33 mcg/0.75 ml: pen-injectors 1, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection transparent, colorless.

0.125 ml – pen-injectors – cardboard packs /complete with needle-1 pc./ – By prescription
0.125 ml – pen-injectors (10 pcs.) – cardboard packs /complete with needles-10 pcs./ – By prescription
0.125 ml – pen-injectors (5 pcs.) – cardboard packs /complete with needles-5 pcs./ – By prescription

Solution for subcutaneous injection transparent, colorless.

0.25 ml – pen-injectors – cardboard packs /complete with needle-1 pc./ – By prescription
0.25 ml – pen-injectors (10 pcs.) – cardboard packs /complete with needles-10 pcs./ – By prescription
0.25 ml – pen-injectors (5 pcs.) – cardboard packs /complete with needles-5 pcs./ – By prescription

Solution for subcutaneous injection transparent, colorless.

0.375 ml – pen-injectors – cardboard packs /complete with needle-1 pc./ – By prescription
0.375 ml – pen-injectors (10 pcs.) – cardboard packs /complete with needles-10 pcs./ – By prescription
0.375 ml – pen-injectors (5 pcs.) – cardboard packs /complete with needles-5 pcs./ – By prescription

Solution for subcutaneous injection transparent, colorless.

0.5 ml – pen-injectors – cardboard packs /complete with needle-1 pc./ – By prescription
0.5 ml – pen-injectors (10 pcs.) – cardboard packs /complete with needles-10 pcs./ – By prescription
0.5 ml – pen-injectors (5 pcs.) – cardboard packs /complete with needles-5 pcs./ – By prescription

Solution for subcutaneous injection transparent, colorless.

0.75 ml – pen-injectors – cardboard packs /complete with needle-1 pc./ – By prescription
0.75 ml – pen-injectors (10 pcs.) – cardboard packs /complete with needles-10 pcs./ – By prescription
0.75 ml – pen-injectors (5 pcs.) – cardboard packs /complete with needles-5 pcs./ – By prescription

Clinical-Pharmacological Group

Recombinant human follicle-stimulating hormone

Pharmacotherapeutic Group

Sex hormones and modulators of the genital system; gonadotropins and other ovulation stimulants; gonadotropins

Pharmacological Action

Recombinant FSH, obtained by genetic engineering from Chinese hamster ovary cells.

It has a gonadotropic effect – stimulates the growth and maturation of the follicle/follicles, promotes the development of several follicles during controlled ovarian hyperstimulation, including for assisted reproductive technology programs.

Pharmacokinetics

After subcutaneous administration, the absolute bioavailability is approximately 70%.

After repeated injections, a threefold accumulation of follitropin alfa in the blood is observed compared to a single injection.

Steady-state concentration is achieved within 3-4 days.

The volume of distribution is 10 L, total clearance is 0.6 L/h.

Indications

Anovulation (including polycystic ovary syndrome (PCOS)) in women in case of ineffectiveness of previous clomifene therapy.

Controlled ovarian hyperstimulation in assisted reproductive technology programs.

Ovarian stimulation in women with severe FSH and LH deficiency (in combination with an LH preparation, in the appropriate dosage form).

Stimulation of spermatogenesis in hypogonadotropic hypogonadism in men (in combination with hCG, in the appropriate dosage form).

ICD codes

Dosage Regimen

Administer Bemfola subcutaneously. The dosage regimen is individualized for each patient based on indication, ovarian response, and semen analysis. Initiate treatment under the supervision of a physician experienced in infertility management.

For anovulatory infertility, start with 75-150 IU follitropin alfa daily. Adjust the dose after 7-14 days and subsequently at 7-day intervals by 37.5 IU increments. Do not exceed 450 IU daily. Continue until adequate follicular development is achieved. Administer hCG (5,000-10,000 IU) 24-48 hours after the last Bemfola injection to finalize follicular maturation.

For controlled ovarian hyperstimulation in ART, start with 150-225 IU daily, beginning on day 2 or 3 of the cycle. Adjust the dose after 5 days based on ovarian response. Continue until sufficient follicles of adequate size are present. Administer hCG for the final follicular maturation trigger.

For ovarian stimulation in severe gonadotropin deficiency, use Bemfola in combination with a luteinizing hormone (LH) preparation. Start with 75-150 IU Bemfola daily. Adjust the dose based on ovarian monitoring.

For stimulation of spermatogenesis in men, first initiate pretreatment with hCG until normal serum testosterone levels are achieved. Then add Bemfola at a dose of 150 IU administered three times per week. Continue combined therapy for at least 4 months. A minimum treatment duration of 18 months may be required to achieve sperm production.

Monitor therapy closely. In women, use ultrasound and measurement of plasma estradiol concentration. In men, monitor semen analysis and serum testosterone. Use the minimum effective dose to achieve treatment goals. Discontinue treatment in cases of excessive ovarian response or signs of impending OHSS.

Adverse Reactions

In women

Immune system disorders very rarely – hypersensitivity reactions, from mild and moderate (skin redness, rash, facial swelling, urticaria, difficulty breathing) to severe, including anaphylactic reactions and shock.

Nervous system disorders very often – headache.

Cardiovascular system disorders very rarely – thromboembolism, usually associated with OHSS.

Respiratory system disorders very rarely – in patients with bronchial asthma, worsening of the course or exacerbation of the disease.

Gastrointestinal disorders often – abdominal pain, heaviness, abdominal discomfort, nausea, vomiting, diarrhea.

Reproductive system and breast disorders very often – ovarian cysts; often – mild and moderate OHSS; infrequently – severe form of OHSS; rarely – complication of OHSS, ectopic pregnancy (in women with a history of fallopian tube diseases), multiple pregnancy.

Local reactions very often – pain, redness, hematoma, swelling at the injection site.

General disorders fever, arthralgia.

In men

Immune system disorders very rarely – hypersensitivity reactions, from mild and moderate (skin redness, rash, facial swelling, urticaria, difficulty breathing) to severe, including anaphylactic reactions and shock.

Respiratory system disorders very rarely – in patients with bronchial asthma, worsening of the course or exacerbation of the disease.

Skin and subcutaneous tissue disorders often – acne.

Reproductive system and breast disorders often – gynecomastia, varicocele.

Metabolism and nutrition disorders often – weight gain.

Local reactions very often – pain, redness, hematoma, swelling at the injection site.

General disorders fever, arthralgia.

Contraindications

Hypersensitivity to follitropin alfa; tumors of the pituitary gland or hypothalamus.

In women: pregnancy; space-occupying lesions or ovarian cysts (not associated with PCOS), gynecological bleeding of unknown etiology, ovarian cancer, uterine cancer, breast cancer; in cases where the goal of therapy cannot be achieved – with developmental anomalies of the genital organs and uterine fibroids incompatible with pregnancy, with primary ovarian failure, premature menopause.

Not used in adolescent girls under 18 years of age.

Use is not indicated after menopause.

In men: in primary hypogonadism (primary testicular failure).

With caution

In patients with porphyria, as well as in the presence of porphyria in relatives.

In women with a history of or currently having thromboembolic disease or in women at high risk of developing thromboembolic complications (presence of thrombosis or thromboembolism in close relatives).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

Not used during breastfeeding.

Pediatric Use

Not used in adolescent girls under 18 years of age.

Geriatric Use

The safety and efficacy of follitropin alfa in elderly patients have not been established.

Special Precautions

Before starting treatment, the fact of marital infertility and possible contraindications to pregnancy should be established.

Concomitant endocrine diseases (hypothyroidism, adrenal insufficiency, hyperprolactinemia, hypothalamic and pituitary tumors) must be excluded.

It is necessary to assess the patency of the fallopian tubes to select the method of ART.

Fallopian tube obstruction should be excluded if the patient is not participating in an in vitro fertilization program.

In patients with porphyria, as well as in the presence of porphyria in relatives, careful monitoring is required during therapy with follitropin alfa.

If the condition worsens or the first signs of this disease appear, discontinuation of therapy may be required.

During therapy with follitropin alfa, assessment of the ovarian status by ultrasound is required – both separately and in combination with the determination of plasma estradiol concentration.

The response to FSH administration may differ among patients, so the minimum effective doses should be used in both women and men.

When prescribing hCG, the possibility of ovarian hyperstimulation syndrome increases, so if an excessive estrogenic response occurs, hCG is not prescribed, and patients are advised to refrain from coitus for at least 4 days.

The likelihood of hyperstimulation can be reduced by aspirating all follicles before ovulation.

The frequency of multiple pregnancy and childbirth during ovulation induction is higher compared to natural conception, with twins being the most common variant in multiple pregnancies.

Multiple pregnancy, especially with a large number of embryos, increases the risk of adverse outcomes for the mother and fetus.

To minimize the risk of multiple pregnancy, careful monitoring of the ovarian response is necessary.

In ART, the risk of multiple pregnancy is mainly associated with the number of transferred embryos, their viability, and the age of the patient.

The frequency of congenital fetal malformations after the use of ART programs may be slightly higher than in natural pregnancy and childbirth.

However, it is unknown whether this is related to parental characteristics (e.g., maternal age, sperm quality) and multiple pregnancy or directly to the ART procedures.

An increased concentration of follicle-stimulating hormone in the serum of men may indicate primary testicular failure.

In this case, therapy with follitropin alfa is not effective, its use is contraindicated.

Drug Interactions

With simultaneous use with other means for ovulation stimulation, an increase in the follicular formation response is possible, while simultaneous desensitization of the pituitary gland with a GnRH agonist may lead to the need to increase the dose of follitropin alfa that causes an adequate ovarian response.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.